Examining the occurrence of disease in first-degree relatives (parents, siblings, children) is a powerful method used to discern genetic versus non-genetic factors leading to disease. Of the various familial connections, sibling comparisons are often more useful than others. While the ultimate tool for parsing genetic from environmental/other causes is a study of identical twins raised in separate environments, this is obviously very rare. Thus, the most commonly used studies in this regard are simple twin studies (because some or most genetic information is shared), followed by sibling studies, because of their unique relationships.
The Sisters of Women with Systemic Lupus Erythematosus (SisSLE) study is an ongoing research effort examining the state of health of the sisters of patients diagnosed with lupus, particularly focusing on the co-occurrence of the same or other autoimmune disorders in this population. Investigations into the heredity of other autoimmune disease, and the likelihood of first-degree relatives developing the same or different conditions have yielded information on various other autoimmune research, with regard to teasing out genetic and other causative factors, and figuring out why some siblings develop the disorder while others do not. Although such information can be invaluable in both research and clinical settings, there is still much work to be performed in the search for a deeper understanding of the autoimmune linkages among first-degree relatives, especially those of patient siblings.
This is difficult to estimate in general, because each autoimmune disease has a different risk profile, which changes based on the relative being considered and the comorbid diseases being examined in relation to the original disorder. That is, this likelihood can vary greatly depending on the principal condition, which other autoimmune conditions we’re considering, and in what population (siblings, twins, parents, children, etc.). For most conditions the risk is generally mild to moderate, with percentage increases in the single digits at most. However, other combinations demonstrate marked upticks in relative risk, which is a commonly used measure of the likelihood of disease development in first-degree relatives.
Also, different studies have indicated varying degrees of relative risk when examining the same conditions, making an accurate estimate of overall incidence and prevalence more difficult. Among the most commonly examined diseases in terms of first-degree relatives and relative risk are celiac, scleroderma, and especially multiple sclerosis. As you’ll note from the links provided, such risk/likelihood can vary widely, for the reasons mentioned above:
Yes, among other things. The general purpose of sibling and other first-degree relative research is to differentiate genetic from non-genetic factors in the development of disease. Such factors include things like environment and lifestyle (especially in behavioral genetics, commonly known as “nature vs. nurture”, which doesn’t really apply here). Some examples are smoking status, obesity and exposure to environmental toxins, among many more. But there are also other considerations such as hormonal input, viral infection and congenital defects; and researchers tend to look for protective effects as well. However, the overarching goal of sibling studies is to determine why one sibling is positive for disease, while the other(s) remain pathology-free, so that this information may be used to advance diagnostic and therapeutic measures. This is true regardless of whether we are considering autoimmune disease or other disorders.
Currently there are at least three ongoing studies involving some aspect of autoimmune disease(s) and sibling diagnoses, which examine generalized autoimmune conditions, systemic rheumatic disease, and lupus (the SisSLE study mentioned above). However, not all of them are still accepting patients. There are of course probably more studies taking place that are not as well advertised as the three found, and certain websites may be able to help you find additional information and resources, such as CenterWatch.com and the NIH’s Clinical Trials website.
As you might imagine, based on what you’ve read so far, there have been many different findings culled from prior sibling and first-degree relative studies investigating autoimmune conditions. It’s not easy to categorize these conclusions in any meaningful or generalized way, because there tends to be such variation in populations examined, methods and analyses used, and specific findings, depending on the exact nature of the research conducted. Not to mention the wide range of disorders studied. Therefore, rather than attempt to outline all the various findings such studies indicate, it would be more helpful to offer multiple links so that you, the reader, can examine them for yourself, prioritizing those most meaningful to your situation:
There do appear to be some common findings across studies, particularly when looking at type-1 diabetes and autoimmune thyroid disease. Such findings have included a disproportionate increase in the latter in siblings of those with the former and other ADs.
Other results have indicated similar issues, with thyroid disease, lupus SLE, multiple sclerosis and rheumatoid arthritis being the most prominently identified conditions. Of these, autoimmune thyroid disease (Graves’ and Hashimoto’s, among others) seems to exhibit the most susceptibility to large increases in disease incidence based on the presence of autoimmune disease in a sibling.
About the Author
Dr. Rothbard is a professional medical writer and consultant based in New York City, specializing in medical education articles targeted at a variety of audiences, from children through clinicians. After leaving medicine, he worked as a biology and medical science educator for several years, before deciding to pursue writing full-time. He may be reached at [email protected].
This blog post was originally published by AutoimmuneMom.com, written by Dr. Rothbard, and first published on Feb 27, 2014.